Enhanced Inhibition of Amyloid Formation by Heat Shock Protein 90 Immobilized on Nanoparticles

As the population ages, an epidemic of neurodegenerativediseaseswith devastating social consequences is looming. To address the pathologiesleading to amyloid-related dementia, novel therapeutic strategiesmust be developed for the treatment or prevention of neural protein-foldingdisorders. Nanotechnology will be crucial to this scenario, especiallyin the design of nanoscale systems carrying therapeutic compoundsthat can navigate the nervous system and identify amyloid to treatit in situ. In this line, we have recently designed a highly simplifiedand versatile nanorobot consisting of a protein coating based on theheat shock protein 90 (Hsp90) chaperone that not only propels nanoparticlesusing ATP but also endows them with the extraordinary ability to foldand restore the activity of heat-denatured proteins. Here, we assessthe effectiveness of these nanosystems in inhibiting/reducing theaggregation of amyloidogenic proteins. Using Raman spectroscopy, wequalitatively and quantitatively analyze amyloid by identifying andsemi-quantifying the Amide I band. Our findings indicate that thecoupling of Hsp90 to nanoparticles results in a more potent inhibitionof amyloid formation when compared to the soluble protein. We proposethat this enhanced performance may be attributed to enhanced release-capturecycles of amyloid precursor oligomers by Hsp90 molecules nearby onthe nanosurface. Intelligent biocompatible coatings, like the onedescribed here, that enhance the diffusivity and self-propulsion ofnanoparticles while enabling them to carry out critical functionssuch as environmental scanning, identification, and amyloid prevention,present an exceptional opportunity for the development of advancednanodevices in biomedical applications. This approach, which combinedactive biomolecules with synthetic materials, is poised to revealremarkable prospects in the field of nanomedicine and biotechnology.

Automated summary

As the population ages, the looming epidemic of neurodegenerative diseases with devastating social consequences is driving the need for novel therapeutic strategies. Nanotechnology, especially in the design of nanoscale systems, is crucial in developing methods to identify and treat neural protein-folding disorders. Recent advancements include the design of a highly versatile nanorobot with a protein coating that enables folding and restoration of heat-denatured proteins, which shows effective inhibition of amyloid formation. Intelligent biocompatible coatings present exceptional prospects for the development of advanced nanodevices in biomedicine and biotechnology.